Methods for predicting the course of a malignant disease

Abstract

The present invention relates to methods of predicting the course of malignant disease and more specifically to methods which use SERPINE2 as a prognostic indicator of disease in cancer patients.

1 . A method for predicting the course of malignant disease in an individual, comprising
 (a) determining levels of expression of SERPINE2 within a patient biological sample and a control biological sample;   (b) comparing the results of step (a); and   (c) correlating the comparison of step (b) to a predicted course of said malignant disease.   
     
     
         2 . The method of  claim 1 , wherein the malignant disease is colorectal carcinoma. 
     
     
         3 . The method of  claim 1 , wherein the malignant disease is hepatocellular carcinoma. 
     
     
         4 . The method of  claim 1 , wherein the malignant disease is pancreatic carcinoma. 
     
     
         5 . The method of  claim 1 , wherein the malignant disease is adult soft tissue sarcoma. 
     
     
         6 . The method of  claim 1 , wherein the malignant disease is a carcinoma except for pancreatic carcinoma. 
     
     
         7 . The method of  claim 1 , wherein the patient biological sample is malignant tissue obtained from said individual. 
     
     
         8 . The method of  claim 1 , wherein the control biological sample is a predetermined standard. 
     
     
         9 . The method of  claim 1 , wherein the control biological sample is an immortalized cell tissue culture. 
     
     
         10 . The method of  claim 1 , wherein the control biological sample is a primary cell tissue culture. 
     
     
         11 . The method of  claim 1 , wherein the control biological sample is non-malignant tissue of the same type as the patient biological sample. 
     
     
         12 . The method of  claim 1 , wherein the patient biological sample is tissue from a metastatic tumor and the control biological sample is tissue from a primary tumor. 
     
     
         13 . The method of  claim 11 , wherein both the patient and control biological samples are obtained from the same individual. 
     
     
         14 . The method of  claim 12 , wherein both the patient and control biological samples are obtained from the same individual. 
     
     
         15 . The method of  claim 1 , wherein the level of expression of SERPINE2 is determined utilizing mRNA. 
     
     
         16 . The method of  claim 1 , wherein the level of expression of SERPINE2 is determined utilizing cDNA. 
     
     
         17 . The method of  claim 1 , wherein the level of expression of SERPINE2 is determined utilizing SERPINE2 protein. 
     
     
         18 . The method of  claim 1 , wherein the level of expression of SERPINE2 is determined utilizing labeled nucleic acids. 
     
     
         19 . The method of  claim 18 , wherein said label is selected from the group consisting of a radiolabel, an enzyme, a chromophore, and a fluorophore. 
     
     
         20 . The method of  claim 1 , wherein the level of expression of SERPINE2 is determined using either northern blot hybridization or a fixed-array of mRNA targets. 
     
     
         21 . The method of  claim 1 , wherein the level of expression of SERPINE2 is determined using either southern blot hybridization or a fixed array of cDNA targets. 
     
     
         22 . The method of  claim 1 , wherein the level of expression of SERPINE2 is determined using either western blot or a fixed array of protein targets. 
     
     
         23 . The method of  claim 1 , wherein the level of expression of SERPINE2 is determined utilizing anti-SERPINE2 antibodies. 
     
     
         24 . The method of  claim 23 , wherein said antibodies are labeled. 
     
     
         25 . The method of  claim 24 , wherein said label is selected from the group consisting of a radiolabel, an enzyme, a chromophore, and a fluorophore. 
     
     
         26 . A method for predicting a relapse of a malignant disease in an individual, comprising
 (a) determining levels of expression of SERPINE2 within a patient biological sample and a control biological sample;   (b) comparing the results of step (a); and   (c) correlating the comparison of step (b) to a predicted course of said malignant disease.   
     
     
         27 . The method of  claim 26 , wherein the malignant disease is colorectal carcinoma. 
     
     
         28 . The method of  claim 26 , wherein the malignant disease is hepatocellular carcinoma. 
     
     
         29 . The method of  claim 26 , wherein the malignant disease is pancreatic carcinoma. 
     
     
         30 . The method of  claim 26 , wherein the malignant disease is adult soft tissue sarcoma. 
     
     
         31 . The method of  claim 26 , wherein the malignant disease is a carcinoma except for pancreatic carcinoma. 
     
     
         32 . The method of  claim 26 , wherein the patient biological sample is malignant tissue obtained from said individual. 
     
     
         33 . The method of  claim 26 , wherein the control biological sample is a predetermined standard. 
     
     
         34 . The method of  claim 26 , wherein the control biological sample is an immortalized cell tissue culture. 
     
     
         35 . The method of  claim 26 , wherein the control biological sample is a primary cell tissue culture. 
     
     
         36 . The method of  claim 26 , wherein the control biological sample is non-malignant tissue of the same type as the patient biological sample. 
     
     
         37 . The method of  claim 26 , wherein the patient biological sample is tissue from a metastatic tumor and the control biological sample is tissue from a primary tumor. 
     
     
         38 . The method of  claim 36 , wherein both the patient and control biological samples are obtained from the same individual. 
     
     
         39 . The method of  claim 37 , wherein both the patient and control biological samples are obtained from the same individual. 
     
     
         40 . The method of  claim 26 , wherein the level of expression of SERPINE2 is determined utilizing mRNA. 
     
     
         41 . The method of  claim 26 , wherein the level of expression of SERPINE2 is determined utilizing cDNA. 
     
     
         42 . The method of  claim 26 , wherein the level of expression of SERPINE2 is determined utilizing SERPINE2 protein. 
     
     
         43 . The method of  claim 26 , wherein the level of expression of SERPINE2 is determined utilizing labeled nucleic acids. 
     
     
         44 . The method of  claim 43 , wherein the label is selected from the group consisting of a radiolabel, an enzyme, a chromophore, and a fluorophore. 
     
     
         45 . The method of  claim 26 , wherein the level of expression of SERPINE2 is determined using either northern blot hybridization or a fixed-array of mRNA targets. 
     
     
         46 . The method of  claim 26 , wherein the level of expression of SERPINE2 is determined using either southern blot hybridization or a fixed array of cDNA targets. 
     
     
         47 . The method of  claim 26 , wherein the level of expression of SERPINE2 is determined using either western blot or a fixed array of protein targets. 
     
     
         48 . The method of  claim 26 , wherein the level of expression of SERPINE2 is determined utilizing anti-SERPINE2 antibodies. 
     
     
         49 . The method of  claim 48 , wherein said antibodies are labeled. 
     
     
         50 . The method of  claim 49 , wherein said label is selected from the group consisting of a radiolabel, an enzyme, a chromophore, and a fluorophore. 
     
     
         51 . The method of  claim 1 , further comprising the correlation of SERPINE2 expression with additional prognostic indicators. 
     
     
         52 . A kit useful for the prognosis of a malignant disease, comprising a fixed array of nucleotide or protein targets wherein at least one target specifically detects SERPINE2. 
     
     
         53 . The kit of  claim 52 , wherein at least one target is at least 12 contiguous nucleotides substantially identical to either the nucleotide sequence in  FIG. 1  or the nucleotide sequence in  FIG. 2 . 
     
     
         54 . The kit of  claim 52 , wherein the protein target is a protein capture agent. 
     
     
         55 . The kit of  claim 53 , wherein the protein capture agent is either a protein with an amino acid sequence set forth in  FIG. 3  or a protein with an amino acid sequence consisting of at least 12 consecutive amino acids in  FIG. 3 . 
     
     
         56 . The kit of  claim 53 , wherein said protein capture agent is an antibody or functional equivalent thereof that binds SERPINE2. 
     
     
         57 . The kit of  claim 53 , wherein said protein capture agent is a SERPINE2 binding partner. 
     
     
         58 . The kit of  claim 52 , further comprising at least one target specifically detecting another gene or gene product useful as a prognostic indicator. 
     
     
         59 . A method for detecting gene or gene products useful as prognostic indicators of a malignant disease, comprising
 (a) determining levels of expression of SERPINE2 within a patient biological sample and a control biological sample;   (b) determining levels of expression of another gene or gene product within a patient biological sample and a control biological sample   (c) comparing the results of step (a) and step (b); and   (d) correlating the comparison of step (c) to predict the usefulness of the gene or gene product as a prognostic indicator of a malignant disease.   
     
     
         60 . The method of  claim 26 , further comprising the correlation of SERPINE2 expression with additional prognostic indicators.